Mentions:
Htr3a KO mice were fed an HFD for 6 weeks from 10 weeks of age and analysed their metabolic phenotypes (Supplementary Fig. 4a). As shown in Fig. 7, Htr3a KO mice were resistant to HFD-induced obesity (Fig. 7a,b). However, glucose tolerance was not improved in Htr3a KO mice, despite the improved insulin sensitivity (Fig. 7c,d). Defective insulin secretion in Htr3a KO mice can explain the discrepancy between glucose tolerance and insulin sensitivity26. As expected, Htr3a KO mice exhibited increased oxygen consumption and heat production compared with their WT littermates (Fig. 7e and Supplementary Fig. 4b). HFD-fed Htr3a KO mice did not exhibit enlarged unilocular lipid droplets in the BAT, which were observed in the BAT of their WT littermates after HFD feeding (Fig. 8a). Thermogenic gene expressions also increased in BAT of Htr3a KO mice (Fig. 8b). Furthermore, mitochondrial biogenesis was increased in BAT of Htr3a KO mice (Fig. 8c,d). These data suggested that the metabolic and histological changes observed in HFD-fed Tph1 AFKO mice could be attributed to the reduced Htr3 activity in BAT. However, WAT of Htr3a KO mice did not exhibit similar changes to Tph1 AFKO after HFD, suggesting the more selective effects of Htr3 in BAT (Figs 7b and 8e).

Mentions:
Htr3a KO mice were fed an HFD for 6 weeks from 10 weeks of age and analysed their metabolic phenotypes (Supplementary Fig. 4a). As shown in Fig. 7, Htr3a KO mice were resistant to HFD-induced obesity (Fig. 7a,b). However, glucose tolerance was not improved in Htr3a KO mice, despite the improved insulin sensitivity (Fig. 7c,d). Defective insulin secretion in Htr3a KO mice can explain the discrepancy between glucose tolerance and insulin sensitivity26. As expected, Htr3a KO mice exhibited increased oxygen consumption and heat production compared with their WT littermates (Fig. 7e and Supplementary Fig. 4b). HFD-fed Htr3a KO mice did not exhibit enlarged unilocular lipid droplets in the BAT, which were observed in the BAT of their WT littermates after HFD feeding (Fig. 8a). Thermogenic gene expressions also increased in BAT of Htr3a KO mice (Fig. 8b). Furthermore, mitochondrial biogenesis was increased in BAT of Htr3a KO mice (Fig. 8c,d). These data suggested that the metabolic and histological changes observed in HFD-fed Tph1 AFKO mice could be attributed to the reduced Htr3 activity in BAT. However, WAT of Htr3a KO mice did not exhibit similar changes to Tph1 AFKO after HFD, suggesting the more selective effects of Htr3 in BAT (Figs 7b and 8e).